{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T11:18:37Z","timestamp":1780399117438,"version":"3.54.1"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T00:00:00Z","timestamp":1424908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"crossref","award":["109366"],"award-info":[{"award-number":["109366"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"crossref"}]},{"name":"F\u00f6rderverein Krebsforschung Saar-Pfalz-Mosel","award":["not numbered"],"award-info":[{"award-number":["not numbered"]}]},{"name":"HOMFOR","award":["not numbered"],"award-info":[{"award-number":["not numbered"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:p>Hyperphosphorylated paratarg\u20107 (pP\u20107) carrier state is the strongest and most frequent molecular risk factor for MGUS, multiple myeloma (MM) and Waldenstr\u00f6m's macroglobulinemia (WM), inherited autosomal\u2010dominantly and, depending on the ethnic background, found in up to one third of patients with MGUS\/MM. Since P\u20107 is the antigenic target of paraproteins that do not distinguish between wtP\u20107 and pP\u20107, we investigated CD4<jats:sup>+<\/jats:sup> T\u2010cell responses in pP\u20107<jats:sup>+<\/jats:sup> patients and controls. Peptides spanning amino acids 1\u201335 or 4\u201331 containing phosphorylated or nonphosphorylated serine17 were used for stimulation. CD4<jats:sup>+<\/jats:sup> cells from 9\/14 patients (65%) showed a pP\u20107 specific HLA\u2010DR restricted response. These results demonstrate that pP\u20107 specific CD4<jats:sup>+<\/jats:sup> cells can mediate help for pP\u20107 specific chronic antigenic stimulation of P\u20107 specific B cells, which might ultimately result in the clonal evolution of a B cell into MGUS\/MM\/WM producing a P\u20107 specific paraprotein. Prerequisites for pP\u20107 specific stimulation of CD4<jats:sup>+<\/jats:sup> cells appear to be both a pP\u20107 carrier state and an HLA\u2010DR subtype able to present and recognize pP\u20107. Our results serve as an explanation for the exclusive autoimmunogenicity of the hyperphosphorylated variant of P\u20107 and for the different hazard ratios of pP\u20107 carriers from different ethnic origins to develop MGUS\/MM\/WM.<\/jats:p>","DOI":"10.1002\/ijc.29478","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T08:34:36Z","timestamp":1423816476000},"page":"1076-1084","source":"Crossref","is-referenced-by-count":10,"title":["<scp>CD4<\/scp><sup>+<\/sup><scp>T<\/scp> cells in chronic autoantigenic stimulation in <scp>MGUS<\/scp>, multiple myeloma and <scp>W<\/scp>aldenstr\u00f6m's macroglobulinemia"],"prefix":"10.1002","volume":"137","author":[{"given":"Frank","family":"Neumann","sequence":"first","affiliation":[{"name":"Jos\u00e9 Carreras Center for Immuno and Gene Therapy Department of Internal Medicine I Saarland University Medical School  Homburg\/Saar Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pfreundschuh","sequence":"additional","affiliation":[{"name":"Jos\u00e9 Carreras Center for Immuno and Gene Therapy Department of Internal Medicine I Saarland University Medical School  Homburg\/Saar Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus D.","family":"Preuss","sequence":"additional","affiliation":[{"name":"Jos\u00e9 Carreras Center for Immuno and Gene Therapy Department of Internal Medicine I Saarland University Medical School  Homburg\/Saar Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Schormann","sequence":"additional","affiliation":[{"name":"Jos\u00e9 Carreras Center for Immuno and Gene Therapy Department of Internal Medicine I Saarland University Medical School  Homburg\/Saar Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Zwick","sequence":"additional","affiliation":[{"name":"Jos\u00e9 Carreras Center for Immuno and Gene Therapy Department of Internal Medicine I Saarland University Medical School  Homburg\/Saar Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Murawski","sequence":"additional","affiliation":[{"name":"Jos\u00e9 Carreras Center for Immuno and Gene Therapy Department of Internal Medicine I Saarland University Medical School  Homburg\/Saar Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Kubuschok","sequence":"additional","affiliation":[{"name":"Jos\u00e9 Carreras Center for Immuno and Gene Therapy Department of Internal Medicine I Saarland University Medical School  Homburg\/Saar Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-387324"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.25.11810"},{"key":"e_1_2_7_4_1","first-page":"829","article-title":"Stomatin\u2010like protein 2 is overexpressed and related to cell growth in human endometrial adenocarcinoma","volume":"17","author":"Cui Z","year":"2007","journal-title":"Oncol Rep"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-09-306076"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24427"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.11.8062"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70234-7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-351668"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-331454"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(94)90269-0"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(90)90142-V"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28233"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-04-1487"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-011-1030-6"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-013-1412-z"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28731"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3107127"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(96)80058-6"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2004.08.005"},{"key":"e_1_2_7_21_1","doi-asserted-by":"crossref","first-page":"3679","DOI":"10.4049\/jimmunol.147.11.3679","article-title":"B cell response to T helper cell subsets. 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